The overall objective of this proposal is to provide proof of concept evidence that a newly-developed prototype laser system can result in dose-sparing of existing influenza (flu) vaccines without any additives. Flu continues to be a significant public health problem and is responsible for up to 3~5 million cases of severe disease and 500,000 deaths a year worldwide. It costs more than 4 billion dollars a year in the US alone. Annual vaccination still remains one of the most cost-effective means to prevent the spread of the virus and decrease flu-caused morbidity and mortality, which, however, creates a huge burden economically, clinically and manufacturally. That is because time of a new vaccine matching the antigen alteration in the circulating virus is relatively short and yet the vaccine demand is massive and continuously increasing drastically every year, in particular, during an outbreak of a new strain or pandemic of flu virus. Vaccine adjuvant can significantly reduce vaccine doses or dosages, reducing the cost enormously. Unfortunately, aluminum-based adjuvant, the only FDA-approved, widely used vaccine adjuvant in the US, failed to provide satisfactory augmentation of immune responses for flu vaccines in humans. We develop a prototype laser system capable of enhancing and prolonging immune responses against protein-based vaccines including season flu vaccine with few side effects. We are exploring this laser vaccine adjuvant (LVA) for dose- sparing of existing seasonal and pandemic flu vaccines. We will investigate whether immune protection elicited by a low dosage of season flu vaccine intradermally or intramuscularly injected into a site of laser exposure is equal to or greater than that induced by a higher dosage of the vaccine injected similarly in Balb/c and C57BL/6 (B6) mice and in minipigs to verify the feasibility of this technology in different animal species with varying skins. A similar study will also be conducted in old and young mice to corroborate that LVA can reduce vaccination doses from two to one in naive young mice and significantly enhance a respondent rate of flu vaccination in old mice. Finally, we will extend the investigation to H5N1 pandemic flu vaccine, protecting mice and ferrets from a lethal challenge of a highly pathogenic avian H5N1 flu virus after one dose of the stockpiled H5N1 vaccine delivered via a combination of LVA and MF59 adjuvant. The laser adjuvant does not need cold chain storage or any modification to the existing vaccines, and it can be used immediately and repeatedly without a limit. These unique characters make this technology ideal for coping with flu vaccine shortages. PUBLIC HEALTH RELEVANCE: Brief illumination of the skin with a safe laser before vaccination may result in dose-sparing of existing influenza vaccines, leading to cost-effective savings in billions of dollars each year for seasonal flu vaccines, and higher vaccine availability in the event of an influenza pandemic.